Multiple dosing of prostaglandin F(2α) or epinephrine on cynomolgus monkey eyes. I. Aqueous humor dynamics

After obtaining baseline intraocular pressure (IOP) measurements for 1 week, prostaglandin (PG) F(2α) (250 μg in 50 μl saline) or epinephrine 2% solution (50 μl) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent tested. Contralateral control eyes received their respective vehicles. PGF(2α) significantly reduced IOP beginning 2 to 3 hr after the first dose, persisting thereafter. A significant (P < 0.05) hypotensive effect remained for at least 10 hr after the first dose and at least 14 hr after the sixth dose. At 4 hr after the seventh dose, the mean reduction was 10.2 ± 3.5 (±SD) mmHg below baseline (P < 0.0025). At this time, there was also a significant (P < 0.01) mean reduction of IOP in the contralateral vehicle-treated eyes of 6.0 ± 3.3 (±SD) mmHg below baseline, which did not appear to be secondary to diurnal fluctuations, repeated tonometry, experimental manipulation, or inadvertent drug transfer. Epinephrine significantly (P < 0.05) reduced IOP beginning 3 hr after the first dose, but this reduction was minimal and not consistent. Neither PGF(2α) nor epinephrine altered aqueous flow as measured by fluorophotometry 2 to 6 hr after the fifth dose. Outflow facility could not be assessed by indentation tonography because IOP was often too low at the time of measurement. Whereas PGF(2α) did not alter pupil size, epinephrine caused significant pupillary dilation. The results of this study demonstrate that multiple topical dosing with PGF(2α) in normal subhuman primate eyes effectively produced a maintained reduction of IOP without evidence of tachyphylaxis or tolerance. These results suggest that PGF(2α), or one of its analogues, warrants a clinical trial in glaucoma patients.